Structural biologist Arun Shukla left his native India for graduate training, as have many other researchers. Unlike most, he worked with three Nobel laureates on two distant continents before returning home. Shukla describes why now is a good time to repatriate to India.

How did you meet your PhD adviser?

While I was in a master's programme in biotechnology at Jawaharlal Nehru University in New Delhi, I was learning about G-protein-coupled receptors (GPCRs), which are involved in almost every physiological process and make up the largest class of potential drug targets. I knew that I wanted to pursue research in this area and attended a fascinating talk by Hartmut Michel, a biochemist at the Max Planck Institute of Biophysics in Frankfurt, Germany, who won the chemistry Nobel in 1988. I spoke with him afterwards and sent him my CV, and he offered me a PhD position.

What was it like at the Max Planck Institute?

Credit: Sarah Iqbal

It was fun. I was working on expressing GPCRs in different cell types. The goal was to crystallize enough protein to use X-ray diffraction to determine the atomic-level structure, so that we could learn how different drugs bind to these receptors. I realized that this was an area that I could work on for the rest of my life.

Did your PhD work make a mark on the field?

I think so. Crystallizing GPCRs was thought to be impossible at the time. GPCRs are highly mobile proteins that sit in the cell membrane, but for crystallography to be successful you need a stable protein. As a result, their structures were not known. Using nuclear magnetic resonance spectroscopy, we were able to determine the structure of a ligand, a hormone bound to a GPCR. Understanding how a ligand bound to a receptor was a big deal, and the work was published in 2008 as a cover article in Angewandte Chemie (J. J. Lopez et al. Angew. Chem. Int. Edn Engl. 47, 1668–1671; 2008). Even today, there are only two such studies in the field. I knew that gaining any insights into GPCR structure would be a landmark and mean a lot to my career.

How did you connect with your next Nobel-laureate mentor?

I was finishing my PhD and knew that I wanted to continue working on GPCRs. Robert Lefkowitz, a biochemist at Duke University in Durham, North Carolina, and future winner of the 2012 chemistry Nobel, is the godfather of GPCRs. I sent him my CV and asked if I could join his lab. Without a formal interview, he wrote back that I was welcome.

Describe your work in such a competitive field.

The goal — to gain insights into GPCR signalling — was pioneering, and there was a risk of getting scooped. In 2013, Lefkowitz, his Nobel co-recipient Brian Kobilka, and I published the structure of β-arrestin, a GPCR-regulating protein (A. K. Shukla et al. Nature 497, 137–141; 2013). Our paper was in the same issue as one from a group that crystallized a different arrestin.

What prompted you to return to India?

I had watched infrastructure and funding prospects improve in the past decade and thought I could run a better group here given the tight US funding situation, so I started applying for positions. I had several offers, and accepted one at the Indian Institute of Technology in Kanpur.

How is it going?

I have the academic freedom to establish GPCR crystallography as a new line of research in this country, with funding from the Indian Department of Science and Technology and a five-year grant from the Wellcome Trust/Department of Biotechnology India Alliance.

Have there been any roadblocks?

It can take weeks to get reagents and consumables from the United States or Europe. We also lose our top PhD graduates overseas so it can be hard to find a good postdoc. My hope is that if we do good work in India, students will realize that they can stay and have high-impact papers.

What was the best piece of advice you received from the Nobel laureates?

Focus on big questions — do things that are cutting edge and will help to shape the direction of the field. We have to make discoveries, not just publish papers.